Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

Abstract

Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue’ diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs’ secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.

Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model

“…Numerous investigations corroborated this hypothesis, indicating the protective activity of the stem cell-released molecules alone (conditioned medium) in the regeneration of the damaged area where, typically, a chronic inflammation condition is present. [33][34][35][36] Significance statement Founding on these theories, in the last decade, more interest has been focused on stem cells secretome and, consequently, on the paracrine effect. [37][38][39] Conditioned medium (CM) consists of extracellular vesicles (EV) and soluble factors.…”

Dental Tissue-Derived Human Mesenchymal Stem Cells and Their Potential in Therapeutic Application

“…Furthermore, dental MSCs may provide the secretome/CM with future regenerative therapeutic applications. Compared with the therapy using dental MSCs, dental MSC-CM, which is cell free, exhibits remarkable biological properties, including higher safety, migration activity, and greater ability of odontoblastic differentiation [ 101 ]. In a recent work, PDLSC-CM was transplanted into surgically created periodontal defects in a rat, and it was found that PDLSC-CM containing extracellular matrix proteins, enzymes, angiogenic factors, growth factors, and cytokines enhanced periodontal regeneration by suppressing the inflammatory response via TNF- α production [ 102 ].…”

Therapeutic Functions of Stem Cells from Oral Cavity: An Update

“…As the paracrine effect is one of the major therapeutic mechanisms of stem cell application, the therapeutic potential of these secretomes derived from dental MSCs on dental disease has been also evaluated [161]. It is revealed that signaling components of the bone morphogenetic proteins (BMPs) and TGF-β pathway seem to be increased in dental MSC-CM.…”